Effective instructional materials can be valuable interventions to improve student interest and achievement in science (National Research Council [NRC], 2007); yet, analyses indicate that many science instructional materials and curricula are fragmented, lack coherence, and are not carefully articulated through a sequence of grade levels (AAAS, 2001; Schmidt et al., 2001). In order to improve student achievement in science, school districts need evidence about the efficacy of instructional materials so they can make sound decisions about their science programs. In addition, science education researchers and curriculum developers can benefit from a better understanding of the characteristics of instructional materials and PD that promote student achievement. The purpose of this study is to examine the efficacy of an intervention that consists of research-based multidisciplinary science curriculum materials for high school students and curriculum-based professional development (PD) for teachers using the materials. The study took place in traditional high schools the state of Washington. Approximately half of the schools were in rural settings in central Washington, the other half were in suburban settings in western Washington. The study sample included nearly 4,000 ninth and tenth grade students nested within 18 high schools. The teacher sample within these 18 schools included 54 teachers. Ninth and tenth grade science teachers in nine treatment schools received curriculum materials and seven days of curriculum-based professional development for each of two years. Teachers in nine comparison schools continued to use extant instructional materials and receive extant professional development (i.e., business-as-usual). A cluster-randomized trial design (Raudenbush et al., 2002) was used where schools were randomly assigned to treatment conditions. Findings showed that research-based science instructional materials with supporting curriculum-based PD have a strong positive effect on classroom instruction and a modest but noteworthy effect on student achievement. One figure is appended.